Faculty Bibliography

Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure and mortality have been reported with the use of these drugs. It is important to have a knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.

BACKGROUND:There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS:We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS:Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS:We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

The COVID-19 pandemic has strained global health care systems in ways that simply could not have been imagined just several months ago. Writing from the heart of New York City - the unfortunate new epicenter of this pandemic - we have been confronted with this new reality head-on. As directors of two major academic cardiac catheterization laboratories in the city, we both have had to operationalize logistical planning of physician and staff redeployments as well as modification of our respective hospital units including conversion of large portions of the catheterization laboratory into COVID-19 intensive care units in order to deal with the surge of COVID-19 patients within the hospital.

Background Detection of flow-limiting left main (LM) coronary artery disease (CAD) has both prognostic and therapeutic implications. Stress testing is the most common method to detect obstructive CAD, however stress markers of LM CAD remain unclear. We set out to identify markers of LM CAD using clinical and stress testing parameters. Methods The population consisted of patients enrolled in the ISCHEMIA trial who underwent non-imaging exercise tolerance testing, stress nuclear imaging or stress echocardiography (SE) and who underwent coronary computed tomography angiography (CCTA). Patients were enrolled based on local determination of moderate or severe ischemia. Those with prior coronary artery bypass grafting were excluded. Multivariate modeling was used to identify predictors of >=50% LM diameter stenosis ("LM disease"), first without and then with stress testing parameters included in the model. Results Of the 5145 patients included (mean age: 63 years, male: 74%), 414 (8%) had LM disease. Predictors of LM disease are shown in the Table. The models were weakly predictive of LM disease (C index 0.643 for clinical model, 0.671 for clinical + stress model). Conclusion In patients with moderate or severe ischemia on stress testing, clinical and stress testing parameters were weakly predictive of LM disease on CCTA. SE-detected TID and ST depression during ETT provided incremental information independent of clinical and other stress modality specific parameters for the prediction of LM disease. [Figure presented]
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Amputation has been known to be a rare adverse event of sodium glucose co-transporter-2 (SGLT2) inhibitors. It remains unclear whether the SGLT2 inhibitor as a class or specific categories of the SGLT2 inhibitors are linked with an increased risk of amputation. The objective of this meta-analysis was to investigate the association between the amputation risk and the use of SGLT2 inhibitors. The main outcome measure was the risk of amputation. Multiple databases were searched up to February 2020 and data extraction was performed. Inclusion criteria were randomized controlled trials (RCTs) which reported risk of amputation with SGLT2 inhibitors over non-SGLT2 inhibitors or placebo. The risk of bias was assessed by Cochrane bias tool. The initial search yielded 1,873 citations and a total of five RCTs were included in the meta-analysis. The five included studies evaluated a total of 39,067 patients with diabetes mellitus, including 21,395 patients on SGLT2 inhibitors. The incidence rate of amputation ranged from 0.36 to 3.18% in the SGLT2 inhibitor group and from 0% to 2.87% in the control group. Follow up duration ranged from 24 weeks to 4.2 years. Use of SGLT2 inhibitors was not associated with significant increase in the risk of amputation as compared with controls (OR: 1.31, 95% CI: 0.92-1.87, I² = 75%). Subgroup analysis showed that neither canagliflozin, empagliflozin, nor dapagliflozin associated with increased risk of amputation. In conclusion, our meta-analysis showed that neither canagliflozin nor other SGLT2 inhibitors increase the risk of amputation. Further studies are required as types of amputations could be heterogeneous and the results may be skewed.

Background Women have been associated with higher rates of recurrent events after percutaneous coronary intervention than men, possibly attributable to advanced age at presentation and greater comorbidities. These factors also put women at higher risk of bleeding, which may influence therapeutic strategies and clinical outcomes. Methods and Results We performed a patient-level pooled analysis of 4 postapproval registries to evaluate sex-related differences in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. HBR required fulfillment of at least 1 major or 2 minor criteria of the Academic Research Consortium definition. Outcomes of interest were major bleeding and major adverse cardiac events (composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis). Of the total 10 502 patients, 2832 (27.0%) were women. The prevalence of HBR was higher in women compared with men (29.0% versus 20.5%, P<0.0001). Women at HBR were older and had more comorbidities, while men at HBR were more often smokers, with prior myocardial infarction and more complex coronary lesions. At 4 years, women at HBR had significantly higher major bleeding compared with men at HBR (10.8% versus 6.2%, P<0.0001); however, this difference was attenuated after multivariable adjustment (hazard ratio, 0.92; 95% CI, 0.41-2.08). Major adverse cardiac event rates between groups were similar (12.2% versus 12.6%, P=0.82) and remained consistent after adjustment (hazard ratio, 0.64; 95% CI, 0.32-1.28). Conclusions The prevalence of HBR was higher in women compared with men, with considerable differences in the distribution of criteria. Women at HBR experienced higher rates of major bleeding but similar major adverse cardiac event rates compared with men at HBR at 4 years.

BACKGROUND:or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS:We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS:Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS:Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).